In vitro sensitivity of human hematopoietic progenitor cells to hyperthermia: critical temperature for cells to survive and its application to in vitro purging.

Normal tissue toxicity is a major concern in cancer therapy. Since the hyperthermic killing of normal human hematopoietic progenitor cells including multilineage progenitor cells (CFU-mix) other than committed granulocyte-macrophage progenitor cells (CFU-GM) is not known, we have studied the thermal sensitivity of various types of human hematopoietic progenitor cells: early and late erythroid progenitors (CFU-E and BFU-E), CFU-GM and CFU-mix using semisolid clonogenic assays. When these progenitor cells were exposed at 42-44 degrees C for 2 h, their thermal sensitivity always appeared to be in the order of CFU-E greater than BFU-E greater than CFU-GM greater than CFU-mix; the CFU-mix was the most tolerant to heat damage. In addition, the survival of human hematopoietic progenitor cells decreased exponentially in exposure time- and temperature-dependent manner. At 44 degrees C human hematopoietic progenitor cells including CFU-mix dropped dramatically in number and therefore were unable to form colonies in vitro after exposure for 2 h. This suggests that 44 degrees C may be the critical temperature for the CFU-mix to survive in vitro. Thus temperatures selected for hyperthermia used to purge residual leukemic cells in remission marrow grafts should be 43 degrees C or lower.